METHODS OF TREATING IgE-MEDIATED DISORDERS COMPRISING THE ADMINISTRATION OF HIGH CONCENTRATION ANTI-IgE ANTIBODY FORMULATIONS

Abstract

The present application relates to methods of treating IgE-mediated disorders comprising the administration of highly concentrated anti-IgE antibody formulations with reduced viscosity that are stable, relatively isotonic and are of low turbidity. The formulations are particularly suitable for subcutaneous administration.

1 . A method of treating an IgE-mediated disorder comprising the administration of a stable, liquid formulation of low turbidity comprising (a) an anti-IgE antibody in an amount of 100 to 260 mg/ml, (b) arginine-HCl in an amount of 50 to 200 mM, (c) histidine in an amount of 10 to 100 mM, (d) polysorbate in an amount of 0.01 to 0.1%, wherein the formulation further has a pH ranging from 5.5 to 7.0, a kinematic viscosity of about 50 cs or less and osmolarity ranging from 200 mOsm/kg to 450 mOsm/kg. 
     
     
         2 . The method of  claim 1 , wherein further the amount of: (a) anti-IgE antibody is about 150 mg/ml, (b) arginine-HCl is about 200 mM, (c) histidine is about 20 mM, (d) polysorbate is about 0.02%, and wherein said formulation has a pH of about 6.0. 
     
     
         3 . The method of  claim 1 , wherein the anti-IgE antibody is selected from the group consisting of rhuMAbE25, rhuMAbE26 and Hu-901. 
     
     
         4 . The method of  claim 1 , wherein the IgE-mediated disorder is selected from the group consisting of hypersensitivity, eczema, urticaria, allergic bronchopulmonary aspergillosis, parasitic diseases, interstitial cystitis, hyper-IgE syndrome, ataxia-telangiectasia, Wiskott-Aldrich syndrome, thymic alymphoplasia, IgE myeloma and graft-versus-host reaction. 
     
     
         5 . The method of  claim 1 , wherein the IgE-mediated disorder is an atopic disorder. 
     
     
         6 . The method of  claim 5 , wherein the IgE-mediated disorder is selected from the group consisting of allergic rhinitis, asthma, allergic asthma, non-allergic asthma, atopic dermatitis and allergic gastroenteropathy. 
     
     
         7 . The method of  claim 5 , wherein the IgE-mediated disorder is selected from the group consisting of food allergy, analphylaxis, contact dermatitis and allergic purpura. 
     
     
         8 . The method of  claim 5 , wherein the IgE-mediated disorder results from exposure to an environmental allergen. 
     
     
         9 . The method of  claim 8 , wherein the environmental allergen is a seasonal, perennial or occupational allergen. 
     
     
         10 . The method of  claim 9 , wherein the environmental allergen is a seasonal allergen. 
     
     
         11 . The method of  claim 10 , wherein the seasonal allergen is pollen. 
     
     
         12 . The method of  claim 8 , wherein the environmental allergen is a perennial allergen. 
     
     
         13 . The method of  claim 12 , wherein the perennial allergen is selected from the group consisting of fungi, feathers and animal and insect debris. 
     
     
         13 . The method of  claim 8 , wherein the environmental allergen is an occupational allergen. 
     
     
         14 . The method of  claim 13 , wherein the occupational allergen is selected from the group consisting of animal and plant antigens. 
     
     
         15 . The method of  claim 13 , wherein the occupational allergen is selected from the group consisting of: drug, detergent, metal and isocyanate. 
     
     
         16 . The method of  claim 5 , wherein the IgE-mediated disorder results from exposure to a non-antigenic allergen. 
     
     
         17 . The method of  claim 16 , wherein the occupational allergen is selected from the group consisting of: smoke, combustion fumes, diesel exhaust particles, sulphur dioxide, exercise, cold and emotional stress. 
     
     
         18 . The method of  claim 1 , wherein the IgE-mediated disorder is hypersensitivity. 
     
     
         19 . The method of  claim 18 , wherein the hypersensitivity reaction results from exposure to food, venom, vaccine, hormone, antiserum, enzyme, latex, antibiotic, muscle relaxant, vitamin, cytotoxin, opiate or polysaccharide. 
     
     
         20 . The method of  claim 19 , wherein the hypersensitivity disorder is selected from the group consisting of anaphylaxis, candidiasis and vasculitis. 
     
     
         21 . The method of  claim 1 , wherein the IgE-mediated disorder is selected from the group consisting of: Churg-Strauss, Syndrome, enteritis, gastroenteropathy, IgE myeloma, inflammatory bowel disease, mucositis, necrotizing enterocolitis and esophagitis.